Randomized study on adjuvant chemotherapy in stage I high-risk ovarian cancer with evaluation of DNA-ploidy as prognostic instrument

Purpose:Adjuvant chemotherapy versus observation and chemotherapyat progression was evaluated in 162 patients in a prospective randomizedmulticenter study. We also evaluated DNA-measurements as an additionalprognostic factor. Patients and methods:Patients received adjuvant carboplatin AUC7 every 28 days for six courses (n = 81) or no adjuvant treatment(n = 81). Eligibility included surgically staged and treated patientswith FIGO stage I disease, grade 1 aneuploid or grade 2 or 3 non-clear cellcarcinomas or clear cell carcinomas. Disease-free (DFS) and disease-specific(DSS) survival were end-points. Results:Median follow-up time was 46 months and progression wasobserved in 20 patients in the treatment group and 19 in the control group.Estimated five-year DFS and DSS were 70% and 86% in thetreatment group and 71% and 85% in the control group. The hazardratio was 0.98 (95% confidence interval (95% CI):0.52–1.83) regarding DFS and 0.94 (95% CI: 0.37–2.36)regarding DSS. No significant differences in DFS or DSS could be seen when thelog-rank test was stratified for prognostic variables. Therefore, data fromboth groups were pooled for the analysis of prognostic factors. DNA-ploidy(P = 0.003), extracapsular growth (P = 0.005), tumor rupture(P = 0.04), and WHO histologic grade (P = 0.04) weresignificant independent prognostic factors for DFS withP < 0.0001for the model in the multivariate Cox analysis. FIGO substage (P =0.01), DNA ploidy (P < 0.05), and histologic grade (P =0.05) were prognostic for DSS with a P-value for the model <0.0001. Conclusions:Due to the small number of patients the study wasinconclusive as regards the question of adjuvant chemotherapy. The survivalcurves were superimposable, but with wide confidence intervals. DNA-ploidyadds objective independent prognostic information regarding both DFS and DSSin early ovarian cancer.     

A 17-year-old with rash, fever, myalgias, and nephritis

Patients on hemodialysis are at increased risk for developing active tuberculosis (TB) after primary infection. Although this increased risk is well documented, the prevalence of TB infection, as indicated by a positive tuberculin skin test (TST), is not well described. End-stage renal disease is also known to be a risk factor for skin test anergy, but the rate of anergy in hemodialysis patients is unclear. We sought to identify rates of anergy and TST positivity in patients at four hemodialysis units in St Louis, Missouri, from June 1996 through August 1996. Data obtained from patients and medical records included age, years on hemodialysis, medical history, and basic laboratory data. Patients without a history of TB or a positive TST had a TST with Tubersol, as well as candida and tetanus controls, placed by the Mantoux method. Tests were read 48 hours later. Of the patients enrolled at these units, 307 of 331 (93%) were evaluated. Patients had a mean age of 58 years (range, 19 to 91 years) and had been on hemodialysis for a mean of 3.7 years (range, 1 week to 18.7 years). Blacks made up 81% of the population. A history of a positive TST was obtained from 24 patients (8%), and an additional seven (2%) had a history of active TB. Of the 276 patients tested, 93 did not respond to either control antigen, but five of these patients had a positive TST, leaving 88 (32%) anergic. Anergy was related to age, immunosuppressive drug use, and the reagents used, but not to urea reduction ratio. Positive TSTs were found in 17 of 188 of nonanergic patients (9%) (6% of all tested patients). Overall, 48 of 307 patients (16%) had a positive TST or history of TB. TB or a positive TST was associated with liver disease and peptic ulcer disease, but not socioeconomic status. All 17 newly identified TST-positive patients received chest radiographs. No new cases of active TB were found. Only two of 17 of these patients (12%) were started on isoniazid (INH) prophylaxis. We identified high rates of TST positivity and anergy in the hemodialysis patients tested. Hemodialysis patients should receive regular TST screening, and INH prophylaxis needs to be more strongly encouraged. Studies are ongoing to define the rate of TST conversion over time.     

Accumulation of methotrexate and methotrexate polyglutamates in lymphoblasts at diagnosis of childhood acute lymphoblastic leukemia: a pilot prognostic factor analysis

Lymphoblasts in bone marrow samples, obtained from 43 children with acute lymphoblastic leukemia at diagnosis, were incubated with 1.0 mumols/L [3H] methotrexate for 24 hours in vitro. Nonexchangeable methotrexate and methotrexate polyglutamates were separated and quantitated. Event-free survival at 5 years was 38% +/- 9% for all 43 patients (27 failures), and 44% +/- 10% for the 35 with non-T, non-B- cell acute lymphoblastic leukemia (20 failures). Of these 35 children, those whose lymphoblasts accumulated more than 100 pmol methotrexate and 500 pmol methotrexate polyglutamates per billion cells experienced better 5-year event-free survival than those whose lymphoblasts did not (65% +/- 12% v 22% +/- 9%, P = .010). This difference characterized "good-risk" patients who were female (P = .014), less than age 7 at diagnosis (P = .005), or had low initial white blood cell counts (less than 20 X 10(9)/L, P = .018). Findings were similar for the 43 children with acute lymphoblastic leukemia and for the "good-risk" children in this total group. Thus, the ability of lymphoblasts to accumulate methotrexate and form methotrexate polyglutamates may be important to the curative properties of current therapy of acute lymphoblastic leukemia in children, particularly for "good-risk" patients. In such patients, inherent rather than acquired drug resistance may be the initial event leading to treatment failure.     

Gene expression signatures differentiate uterine endometrial stromal sarcoma from leiomyosarcoma

ObjectiveEndometrial stromal sarcoma (ESS) and leiomyosarcoma (LMS) are the two most common uterine sarcomas, but both are rare tumors. The aim of the present study was to compare the global gene expression patterns of ESS and LMS.MethodsGene expression profiles of 7 ESS and 13 LMS were analyzed using the HumanRef-8 BeadChip from Illumina. Differentially expressed candidate genes were validated using quantitative real-time PCR and immunohistochemistry.ResultsUnsupervised hierarchical clustering using all 54,675 genes in the array separated ESS from LMS samples. We identified 549 unique probes that were significantly differentially expressed in the two malignancies by greater than 2-fold with 1% FDR cutoff using one-way ANOVA with Benjamini–Hochberg correction, of which 336 and 213 were overexpressed in ESS and LMS, respectively. Genes overexpressed in ESS included SLC7A10, EFNB3, CCND2, ECEL1, ITM2A, NPW, PLAG1 and GCGR. Genes overexpressed in LMS included CDKN2A, FABP3, TAGLN, JPH2, GEM, NAV2 and RAB23. The top 100 genes overexpressed in LMS included those coding for myosin light chain and caldesmon, but not the genes coding for desmin or actin. CD10 was not overexpressed in ESS. Results for selected genes were validated by quantitative real-time PCR and immunohistochemistry.ConclusionsWe present the first study in which gene expression profiling was shown to distinguish between ESS and LMS. The molecular signatures unique to each of these malignancies may aid in expanding the diagnostic battery for their differentiation, and may provide a molecular basis for prognostic studies and therapeutic target discovery.     

Clinical (stage III) as compared to subclinical intrapelvic extrauterine tumor spread in endometrial carcinoma: A clinical and histopathological study of 175 patients

One hundred and seventy-five patients with endometrial cancer, seen in the Norwegian Radium Hospital from 1960 to 1977, had tumor extension outside the uterus but not outside the true pelvis. One hundred and eight of these patients had clinical stage III disease and in 67 patients, originally classified as stage I or stage II, the intrapelvic extrauterine tumor spread was first detected at surgery or at histopathological examination of the operation specimen. The 40% 5-year-actuarial survival of the latter group differed significantly from the 16% found in clinical stage III (P < 0.001). This must be largely contributed to the fact that radical surgery could only be performed in 13% of the clinical stage III group as compared to 70% in the group of patients with subclinical extrauterine disease. Surgical eradication of all macroscopic tumor was of major prognostic importance for patients with clinical stage III, resulting in an actuarial 5-year survival of 41%, nearly identical to 42% for the group of patients with subclinical extrauterine tumor extension. Adjuvant progestagen therapy seemed to be of some benefit, but the need, however, for a more effective systemic treatment, possibly using cytotoxic drugs, is evident.